The protein tyrosine phosphatase (PTP) family of enzymes consists of more than 500 structurally diverse proteins which have in common the highly conserved 250 amino acid PTP catalytic domain, but which display considerable variation in their non-catalytic segments (Charbonneau and Tonks, Annu. Rev. Cell Biol. 8:463-493 (1992); Tonks, Semin. Cell Biol. 4:373-453 (1993)). This structural diversity presumably reflects the diversity of physiological roles of individual PTP family members, which in certain cases have been demonstrated to have specific functions in growth, development and differentiation (Desai et al., Cell 84:599-609 (1996); Kishihara et al., Cell 74:143-156 (1993); Perkins et al., Cell 70:225-236 (1992); Pingel and Thomas, Cell 58:1055-1065 (1989); Schultz et al., Cell 73:1445-1454 (1993)). Although recent studies have also generated considerable information regarding the structure, expression and regulation of PTPs, the nature of the tyrosine phosphorylated substrates through which the PTPs exert their effects remains to be determined. Studies with a limited number of synthetic phosphopeptide substrates have demonstrated some differences in substrate selectivity of different PTPs (Cho et al., Protein Sci. 2: 977-984 (1993); Dechert et al., Eur. J. Biochem. 231:673-681 (1995)), and have indicated preferences for certain amino acid residues at particular positions around the phosphorylated tyrosine residue (Ruzzene et al., Eur. J. Biochem. 211:289-295 (1993); Zhang et al., Biochemistry 33:2285-2290 (1994)). This indicates that PTPs display a certain level of substrate selectivity in vitro, although the physiological relevance of the substrates used in these studies is unclear.